To determine the difference in occurrence of wet desquamation on axillary skin with use of beclomethasone dipropionate spray

Study participants were randomized to two groups. One group received beclomethasone dipropionate spray on irradiated axilla (200 mcg) seven days a week from day one of radiation therapy. Steroid spray was stopped after development of wet desquamation. The other group was not allowed to apply anything in the irradiated area. Both groups were instructed against using soap, oil, or cream in treatment area; shaving in the irradiated area; and wearing anything other than loose cotton clothing. A clinical examination was done weekly while on treatment.

• The study sample (N = 60) was comprised of patients with breast cancer who were receiving loco-regional radiation therapy to the axilla.
• Median age of the steriod group (n = 30) was 44.6 years, with a range of 28–60 years. Median age of the control group (n = 30)  was 45.9 years, with a range of 29–60 years.
• ER/PR-positive patients were started on tamoxifen 20 mg daily.

The study used a randomized controlled trial design.

• Radiation-induced skin reaction was graded weekly in terms of erythema, dry desquamation, and wet desquamation until the end of prescribed 50 Gy dose and one month after completion of radiation therapy. Specific method of measurement not reported.
• Chi-square test was used to see the statistical significance of the difference in wet desquamation on the axillary skin between two arms of the study.

Wet desquamation of axillary skin at the end of radiation developed in 13.33% of patients in the steroid group and 36.66% of patients in the control group (p = 0.0369). There was no significant difference in median dose of radiation causing wet desquamation (42 versus 43.54 Gy).

Topical steroid (beclomethasone dipropionate spray) for skin during radiation may reduce risk of wet desquamation of the skin.

• No specific grading scale appears to have been used.
• No inter- rater reliability testing done.
• Patients were treated on a telecolbalt unit. A 6 MV photon unit has better skin sparing properties. The d-max of a telecolbalt unit is 5 mm versus 15 mm in a 6 MV photon unit. Findings may not be as applicable to 6 MV photon treatment units.
• Patient compliance with skincare instructions were not discussed.
• The sample size was small, with less than 100 patients.

• Tranexamic acid (TA) dose of 1 g every six hours
• Patients receiving induction were given continuous cytarabine 100 mg/m²/day for seven days with daunorubicin 45 mg/m²/day for three days. If remission failed, they were treated with a second cycle of the same. After remission, they received consolidation of cytarabine 3 g/m² twice daily for six days. Patients aged 51–65 years received consolidation of cytarabine 2 g/m².
• Patients aged 66–75 years received induction of daunorubicin 30 mg/m² and consolidation of cytarabine 500 mg/m².
• Platelet count equation = x10⁹/L
• Severity of bleeding was scored on a scale of 0–3 (0 = no bleeding; 1 = few minor mucosal or cutaneous bleeds; 2 = extreme mucosal or cutaneous bleeds; 3 = major bleeding episodes, including gastrointestinal bleed, hematuria, hemoptysis, retinal, or central nervous system bleed irrespective of transfusions required).
• Patients were examined daily.
   

• N = 38
• AGE = 19–71 years
• KEY DISEASE CHARACTERISTICS: Patients with acute myeloid leukemia (AML) during induction (16 in TA group, 22 in placebo group) or consolidation (10 in TA group, 8 in placebo)
• OTHER KEY SAMPLE CHARACTERISTICS: Patients started with a platelet count of less than 20 or a falling trend and less than 50. Treatment was continued until platelet count was greater than 20 on at least two consecutive counts. Patients were excluded if they had a recent thromboembolic event, evidence or suspicion of thromboembolism, or lab signs of disseminated intravascular coagulation. Pooled platelets were given irrespective of count but only when clinically significant bleeding occurred. Packed red blood cells (RBCs) were transfused to maintain greater than 9 g/dL.

• LOCATION: Israel, 1990–1992

• Randomized, placebo-controlled, double-blind study

• Efficacy of TA to reduce bleeding and platelet transfusions during treatment of AML

During induction, there was no difference between the study and control regarding period of thrombocytopenia less than 20, number of bleeding episodes, number of platelet or RBC transfusions, or score of bleeding events. During consolidation, there was significantly less bleeding in the TA group, resulting in less platelets (3.7 +/- 4.1 [p < .05]); there was no significant difference in the number of RBCs transfused. No thromboembolic event or fatal bleeds occurred in either group.
 

• Small size
• Author’s discussion: Lack of benefit during induction could be because of more complex coagulopathy in induction phase, possibly because of more blasts present at induction versus consolidation.
• The TA dose was too low with sub-therapeutic drug levels during induction.
   

To evaluate the effects of prophylactic minocycline on skin toxicities associated with epidermal growth factor receptor inhibitor (EGFRI) treatment

• N = 96
• MEAN AGE = 66.5 years
• AGE RANGE = 34–83 years
• MALES: 59%, FEMALES: 41%
• KEY DISEASE CHARACTERISTICS: All patients had advanced pancreatic cancer.

• SITE: Single site  
• SETTING TYPE: Outpatient  
• LOCATION: Japan

PHASE OF CARE: Active antitumor treatment

• Retrospective

• Common Terminology Criteria for Adverse Events (CTCAE)

Significantly fewer patients who had received prophylactic minocycline developed an acneiform rash (p < 0.001). No differences existed between groups in incidence of rash of grade 2 or higher, and no difference existed between groups in the incidence of paronychia or xerosis.

The findings suggest that prophylactic minocycline may reduce the incidence of low-grade acneiform rash among patients receiving erlotinib and gemcitabine.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• No information regarding actual use of topical steroids was included.

The findings suggest that prophylactic minocycline might be helpful in preventing low-grade acneiform rash among patients receiving EGFRIs; however, it did not appear to have any beneficial effect in terms of the development of more severe skin effects. The study design limits the strength of this evidence. Skin toxicities associated with EGFRIs have been well documented, and little evidence exists regarding interventions that are effective to prevent and treat them. Further well designed research in this area is needed.

To evaluate the efficacy of antibiotic prophylaxis with tosufloxacin or moxifloxacin in adult patients (aged 16 years or older) with hematologic malignancies who were treated with chemotherapy that induced neutropenia and had an absolute neutrophil count less than 500/mcL for five days or longer

From 2004–2006, patients were treated with prophylactic tosufloxacin 150 mg three times daily, and from 2007–2008, patients were treated with prophylactic moxifloxacin 400 mg daily. All patients in both groups were treated with prophylactic antifungal therapy with either fluconazole or itraconazole.

• N = 349 episodes (270 in the tosufloxacin group and 79 in the moxifloxacin group) in 161 patients (116 in the tosufloxacin  group and 45 in the moxifloxacin group)  
• MEAN AGE = 50.7 years in the tosufloxacin group and 53.5 years in moxifloxacin group
• MALES: 57.8% in the tosufloxacin group and 57.8% in the moxifloxacin group, FEMALES: 42.2% in the tosufloxacin group and 42.2% in the moxifloxacin group
• KEY DISEASE CHARACTERISTICS: All patients in the tosufloxacin group and the moxifloxacin group had hematologic malignancies including acute myeloid leukemia (AML) (64.4% and 62%, respectively), lymphoma (9.6% and 10.1%, respectively), acute lymphocytic leukemia (ALL) (15.2% and 5.1%, respectively), and other (10.7% and 22.8%, respectively). More patients had ALL in the tosufloxacin group compared with the moxifloxacin group (p = 0.021). About 7% of patients in both groups were autologous hematopoietic cell transplant recipients.
• OTHER KEY SAMPLE CHARACTERISTICS: Excluded patients included allogeneic stem cell transplant recipients, patients treated with palliative chemotherapy, patients who had a fever or documented infection at the start of chemotherapy, and patients who received antibiotics five days prior to admission.

• SITE: Single site   
• SETTING TYPE: Inpatient   
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

• Retrospective

• Fluoroquinolone resistance was determined according to criteria set forth in “Performance Standards for Antimicrobial Susceptibility Testing”, approved by the U.S. National Committee for Clinical and Laboratory Standards.
• Clostridium difficile-associated diarrhea (CDAD) was defined as a positive Clostridium difficile toxin A assay in the setting of loose stools or watery diarrhea.
• The diagnostic criteria for proven, probable, and possible fungal infection were based on the revised European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria.

Comparison of moxifloxacin to tosufloxacin demonstrated a significantly decreased cumulative incidence of febrile neutropenia (74.7% [59 of 79] and 81.1% [219 of 270], respectively, p = 0.044]; increased incidence of fungal infection in the moxifloxacin group (10.1% compared to 4.1% in the tosufloxacin group, p = 0.048); and no cases of CDAD in either group. No significant difference was seen between groups for the mean duration of neutropenia (17.6 days and 17.9 days, respectively, p = 0.853); documented infection (20.3% and 25.9%, respectively, p = 0.373); mortality (0% and 1.9%, respectively, p = 0.592); or fluoroquinolone-resistant infections (7.6% and 9.3%, respectively, p = 0.823). A subgroup analysis of patients with AML showed a higher incidence of febrile neutropenia in the tosufloxacin group (94.1% versus 71.1%, p = 0.013), perhaps related to the observation that the patients with AML had a longer duration of neutropenia (mean = 20.6 days) than the other patients (mean = 13 days) (p < 0.01). A second subgroup analysis showed that moxifloxacin was more effective in preventing febrile neutropenia in patients with neutropenia lasting 15 days or longer (incidence: 73.8% and 89.7%, respectively, p = 0.008) and had no effect on the incidence in patients with neutropenia lasting 14 days or less (p = 0.930).

Moxifloxacin was more effective than tosufloxacin in preventing febrile neutropenia in patients with AML who were most likely to have a longer duration of neutropenia (15 days or longer). No differences in the incidence of documented infections, fluoroquinolone-resistant infections, or overall mortality were observed.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: The major study limitation is that it's a nonrandomized, retrospective study with data collected from two different time periods (tosufloxacin data from 2004–2006 and moxifloxacin data from 2007–2008). Another potential limitation, although presumed to be minor, is the risk of variation in the degree of patient compliance with oral prophylaxis.

Antibiotic prophylaxis with moxifloxacin is more effective than tosufloxacin in reducing the incidence of febrile neutropenia in high-risk patients who are expected to have a long duration of neutropenia. However, moxifloxacin was associated with more fungal infections. Nurses need to educate and counsel patients regarding antibiotic prophylaxis to enhance adherence, appropriate side effect reporting, and self-monitoring for signs of infection.

To investigate the potential role of pregabalin in the prevention of chemotherapy-induced neuropathy

Patients were randomized to receive placebo or pregabalin 75 mg twice daily starting on the first night of chemotherapy and throughout 12 weeks of chemotherapy. In week 13, the dose was reduced to once daily at bedtime. Patients were instructed to use acetaminophen or oxycodone as needed for breakthrough pain. For the first six days, pain severity and analgesic use were obtained daily; on day 8, they were obtained prior to each subsequent paclitaxel treatment; and they were obtained for six months 30 days after the completion of paclitaxel treatment.

• N = 41 
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer receiving adjuvant or neoadjuvant paclitaxel 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with a history of peripheral neuropathy, prior exposure to neurotoxic chemotherapy, or diabetes were excluded.

• SITE: Multi-site  
• SETTING TYPE: Outpatient
• LOCATION: New York

PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled trial

• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QLC)-CIPN20 
• Common Terminology Criteria for Adverse Events (CTCAE), version 4.0

No differences existed between groups in worst, average, or least pain scores, or in analgesic use. No differences existed in the motor neuropathy or autonomic neuropathy subscale scores of the EORTC instrument. No significant differences were observed in adverse events.

The findings did not support any effect of pregabalin for the prevention of chemotherapy-induced neuropathic symptoms.

• Small sample (< 100)
• The doses of pregabalin used here may have been insufficient to show an effect.

Professional guidelines have suggested that gabapentinoids may be considered as an option to treat chemotherapy-induced neuropathy, although their effectiveness has not been established. This study provides limited evidence to suggest that pregabalin, a type of gabapentinoid, is effective for the prevention or reduction of paclitaxel-induced neuropathic symptoms. Given these results, it may not effectively treat established neuropathic symptoms. Currently, limited treatment options exist for the prevention or management of chemotherapy-induced peripheral neuropathy. Nurses need to be aware of chemotherapy agents that have neurotoxic effects, and monitor patients for early detection of such effects to identify the need for potential treatment dose modification.

To evaluate the efficacy of ​hydromorphone-OROS (HM-OROS) in the treatment of sleep disturbances associated with cancer-related pain

Patients took an equianalgesic dose of HM-OROS for two weeks. The dose of HM-OROS was individualized and based on the total dose of previous opioids that were administered on the last day of the screening phase.

• N = 82  
• MEDIAN AGE = 56.1 years (SD = 11.2 years)
• MALES: 67.9 %, FEMALES: 32.1%
• KEY DISEASE CHARACTERISTICS: Patients with cancer; ≥ 20 years of age; cancer pain ≥ 4 on a numeric rating scale (NRS); sleep disturbance ≥ 4 NRS; using oral opioids for cancer-related pain management
• OTHER KEY SAMPLE CHARACTERISTICS: 81.1% stage IV cancer; colorectal 11%; lung 9.5%; pancreas 9%; stomach 8%; breast 7%; 75% prior chemotherapy, radiation, or surgery

• SITE: Multi-site
• SETTING TYPE: Outpatient facility at a university
• LOCATION: Korea

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

Multicenter, prospective, open-label study with a pre- and post-test

• Sleep disturbance NRS
• Number of times awake after sleep onset
• Pain score
• Need for analgesia for pain prior to bedtime to facilitate sleep
• Korean Brief Pain Inventory (K-BPI)

• The NRS pain score was reduced from 5.3 to 4.1 (p < 0.01).
• The NRS sleep disturbance score was reduced from 5.9 to 4.1 (p < 0.01).
• 26.8% of participants reported a 50% improvement in sleep disturbance, 58.5% reported a 30% improvement in sleep disturbance, and 85% reported an improvement of 10%.
• The K-BPI showed that pain, mood, walking ability, normal work, and sleep improved. The mean sleep score changed from 5.9 to 4.2 (p < 0.01).

HM-OROS improved sleep disturbances in patients with moderate to severe cancer-related pain.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• Subject withdrawals ≥ 10%
• Other limitations/explanation: There was a very high initial number of participants that was reduced by 82 (50%). The initial sample described included 190 participants.

HN-OROS may be an effective drug to treat cancer-related pain and improve sleep disturbance.

• Both the control and intervention groups received regular antiemetics.
• The intervention group also received acupressure training, and patients were instructed to perform the finger acupressure maneuver for five minutes on the P6 point at least three times per day before chemotherapy and mealtimes or as needed.
• Both groups received frequent nursing visits and consultations. The intervention was given with first cycle of 5-fluorouracil and cisplatin chemotherapy.

• This study consisted of 40 patients, 20 in the control group and 20 in the intervention group.
• Patients were 47–52 years old.
• All participants were postoperative patients with gastric cancer.

The study took place in a university medical center in metropolitan South Korea. Participants were on inpatient oncology wards.

This study had a nonequivalent control group design for a single cycle of chemotherapy.

• Demographic data, including family background, diagnosis and treatment, and assessment of nausea and vomiting, were recorded.
• The Rhode’s Index of Nausea, Vomiting and Retching was translated into Korean and back-translated to English to ensure equivalency.
• Patients recorded in daily logs their ratings of nausea experience using a four-point scale and intensity of nausea experience during the past 24 hours.

Significant differences existed between the control and intervention groups in the severity of nausea and vomiting, duration of nausea, and frequency of vomiting.

• Self-report has some degree of measurement error.
• Generalizability is limited because of regional study and small sample size.

STUDY PURPOSE: To evaluate the effects of massage and aromatherapy massage on symptoms in people with cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 19, 5 in meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,274
• SAMPLE RANGE ACROSS STUDIES: 20–144
• KEY SAMPLE CHARACTERISTICS: Varied tumor types, varied settings and phases of care

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Palliative care

Results of the meta-analysis showed no significant differences between massage and no massage for pain, depression, fatigue, or nausea. A meta-analysis of three studies showed significantly lower state anxiety with massage (MD = 18.6, p = 0.0003); however, all studies had very small samples and a high risk of bias. At longer follow-up, no differences were reported between groups in anxiety.

Insufficient evidence exists to show a benefit of massage therapy with or without aromatherapy for the relief of multiple symptoms in people with cancer.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• Low sample sizes

Evidence regarding the effects of massage and aromatherapy massage on various patient symptoms did not show substantial clinical benefit, and evidence is insufficient. However, massage is generally a very low-risk intervention that may provide very short-term benefits for some patients. Additional well-designed research is needed to determine the role of this type of intervention as part of symptom management among patients with cancer at various times in the cancer trajectory.

To evaluate the safety and efficacy of sublingual fentanyl orally disintegrating tablets for breakthrough cancer-related pain

The trial had several phases. In the initial observation phase over four consecutive days, pain intensity and pain relief were evaluated. Patients who showed an analgesic effect for opioid for breakthrough episodes were entered into the titration phase. In the titration phase (no more than 21 days long), patients received 100 mcg of sublingual fentanyl for the first breakthrough episode. The dose was increased by 100 mcg until the optimal dose was determined. Effectiveness was defined as no needed additional dose, and pain scores at 30 and 60 minutes were reduced by at least 18 mm or a third of pain levels prior to administration. Patients for whom optimal dose was determined were entered into the 21-day, double-blinded treatment phase in which three random breakthrough episodes were treated with a placebo for comparison. This was followed by a 12-week extended treatment phase. All pain scores were recorded by subjects in a diary.

• N = 37 (double-blinded phase), 13 (completed extended treatment )
• MEAN AGE = 66 years (SD = 9.2 years)
• MALES: 59.5%, FEMALES: 40.5%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types; lung and colon most prevalent
• OTHER KEY SAMPLE CHARACTERISTICS: The median Visual Analog Scale pain score at baseline was 72.9.

• SITE: Multi-site  
• SETTING TYPE: Multiple settings  
• LOCATION: Japan

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Open-label titration, double-blinded, placebo-controlled, comparative phase trial with a 12-week extended treatment phase

• 100 mm Visual Analog Scale (VAS) for pain severity (pain measured at 15, 30, and 60 minutes during breakthrough episodes)
• Patient global evaluation of relief and satisfaction on five-point scale

Overall, 90.5% of participants were titrated to an effective dose. Pain at 30 and 60 minutes during breakthrough episodes was significantly better with the sublingual fentanyl oral dissolving tablets compared to a placebo (p < 0.0001). No subjects discontinued the trial because of adverse drug effects. In the extended treatment phase, 50% of participants had dose reductions because of somnolence. Opioid analgesics were changed in 68.8% of patients because of uncontrolled pain or adverse events. The most common titrated dose was 300 mcg. The number of days needed to obtain an effective titrated dose ranged from 1–21 days with a median of three days.

Sublingual oral fentanyl dissolving tablets were effective in reducing breakthrough pain compared to a placebo.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement/methods not well described
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Neither the timing of pain measures nor how multiple measurements were handled for the analysis were described. There was no clear description of changes in baseline analgesia or how this was handled in the analysis.

Transmucosal opioids such as sublingual fentanyl oral dissolving tablets were effective in treating episodes of breakthrough pain. In this study, patients received this medication for extended periods, demonstrating few side effects over time.

To test the efficacy and safety of oral fentanyl in doses estimated from basal oral morphine for breakthrough pain

There was an initial observation phase in which breakthrough pain episodes were evaluated. Patients who showed effects from oral morphine entered the investigation phase. The investigation phase included three periods in which two different doses of fentanyl orally disintegrating tablets (FTs) and active controls were investigated in a random order. The dose of the FTs was determined by a conversion ratio of 1:25 for low-dose morphine and 1:50 for high-dose morphine in the observation phase. There were three episodes of breakthrough pain in each period of the investigation. FTs were given twice, and the placebo was given once. Oral morphine was used in the observation period and was given as an active control. Some studies have shown that effective doses of FTs for breakthrough pain did not correlate to round-the-clock opioid doses.

• N = 47  
• MEAN AGE = 59.1 years (range = 37–80 years)
• MALES: 60.8%, FEMALES: 39.2%
• KEY DISEASE CHARACTERISTICS: Various tumor types with lung cancer most common
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were receiving daily opioid analgesics and oral morphine to treat breakthrough pain at least once every two days.

• SITE: Single site  
• SETTING TYPE: Not specified    
• LOCATION: Japan

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Randomized, crossover, double-blinded, placebo-controlled trial with a nonblinded active drug

• Visual Analog Scale (VAS) for pain at 30 and 60 minutes during breakthrough episodes

FTs were better than a placebo for all patients (p < 0.02) and better than the oral morphine control (p < 0.001) at 30 minutes. At 60 minutes, FTs also were better than a placebo (p < 0.001). Nine subjects had adverse reactions. The most common reactions were constipation, nausea, and somnolence. One had nausea and vomiting, and one experienced respiratory depression. A temporary suspension of the investigation drug was initiated in both of these cases.

The findings of this study demonstrated that the method of dose determination used here was safe in the majority of cases, more effective than a placebo, and as effective as oral morphine for breakthrough pain.

• Small sample (< 100)
• Subject withdrawals ≥ 10%

The dose of FTs for breakthrough pain is usually determined by titrating effective doses over a period of time. During titration, the patient may have less than optimal pain control. This study provided a method of dose determination that may be useful and more timely.